Ironwood Progresses sGC Stimulator Platform with Positive Top-Line Phase I Data on IW-1973

Ironwood Pharmaceuticals, Inc.

announced today positive top-line data from a Phase I study of IW-1973, its lead investigational soluble guanylate cyclase (sGC) stimulator. In the study, IW-1973 demonstrated cardiovascular pharmacodynamic effects, extensive tissue distribution, proof of mechanism for sGC stimulation, and a dose range that was well tolerated in healthy volunteers. The totality of clinical and preclinical data generated to date strongly support continued development of IW-1973 as a potential once-daily oral therapy. Ironwood intends to initiate a Phase Ib multiple ascending dose study of IW-1973 in the fourth quarter of 2015. This study will inform the selection of doses and priority indications for the Phase II program, which will focus on areas with the highest unmet need and optimal path to market. Ironwood intends to initiate at least two Phase II proof of concept studies for IW-1973 in 2016. "Soluble guanylate cyclase is a fundamental regulator of blood flow, inflammation and fibrosis that is found in a wide range of human tissues – this is why sGC stimulators offer such breadth of therapeutic potential in cardiovascular disease, fibrosis, muscular dystrophy and other disorders," said Mark Currie, Ph.D., chief scientific officer and president of research and development at Ironwood. "We look forward to leveraging our established expertise in guanylate cyclases to investigate how the unique properties of IW-1973 observed thus far, such as distribution into target tissues, may allow us to expand the potential of the sGC stimulator class in cardiovascular and other serious diseases." The randomized, double-blind, placebo-controlled, single ascending dose Phase I study enrolled 46 healthy volunteers. Participants were randomized 3:1 to receive a single dose of IW-1973 or placebo administered via an oral capsule. Top-line clinical data were consistent with preclinical findings and included cardiovascular pharmacodynamic effects, dose-proportional pharmacokinetics, biomarker-based confirmation of target engagement, and evidence of extensive distribution to tissues. No serious adverse events were reported. Reported adverse events were consistent with the mechanism of action. Data from clinical and preclinical studies of IW-1973 are expected to be presented at a future medical conference.